Résumé :
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Myotonic dystrophy (DM1) is caused by abnormal expansion of a polymorphic (CTG)n repeat, located in the DM protein kinase gene. Respiratory problems have long been recognized to be a major feature of DM1 disease and are probably the main factors contributing to mortality. Since several pulmonary impairments are associated with phrenic nerve and diaphragm dysfunction, we examined the diaphragm and the respiratory neural network in a reliable animal model of human myotonic dystrophy disease. The morphological and morphometric analysis of adjacent diaphragm muscle sections labeled with rhodamine alpha-bungarotoxin and neurofilament antibody revealed that the diaphragm end-plates had significantly smaller size and less complex shapes in DM1 mice than in control. Moreover, the mean density of ACh receptors on the postsynaptic membrane is significantly decreased in DM1 mice. The alterations observed in DM1 neuromuscular junctions indicate a possible denervation of diaphragm muscle. The analysis of both semi and ultra- thin sections taken from the middle trunk of phrenic nerve demonstrated there is a severe and significant decrease in the number of unmyelinated fibers in DM1 mice, however, there is no loss in the number of myelinated fibers. Also no pathological signs or loss in neuronal cells are detected either in medullary respiratory centers or in cervical spinal cord motor neurons. The absence of loss in the number of myelinated fibers in the middle trunk of phrenic nerve led to conclude that the denervation of end-plates is due to distal or intramuscular nerve degeneration. Since the neuromuscular junction are involved in the transmission of action potentials and the afferent phrenic unmyelinated fibers control the inspiratory activity, our results suggest that the respiratory impairment associated with myotonic dystrophy disease could be partially due to the pathological alterations in neuromuscular junctions and phrenic nerves.
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